This research program combines biomedical engineering efforts at Riverside Research Institute (RRI) and biological and medical investigations at Cornell University Medical College (CUMC). The ultimate objectives of the research are: 1) to develop reliable ultrasonic techniques for treating ocular tumors that threaten life and sight; and 2) to assure the safe use of promising new diagnostic ultrasound techniques that promise perhaps revolutionary advances for combatting ocular diseases. Both objectives involve comprehensive, scientific investigations of how ultrasonic energy modifies tissue. Therapy investigations involve the development of intense, short-term ultrasound exposures to treat tumors before blood-flow cooling and attendant uncertainties become significant. Special ultrasound transducers will be developed to reliably induce asymmetric lesions for producing efficient lesion matrices that cover extensive tumor volumes. A comprehensive computer simulation provides a model of relevant beam propagation and tissue heating. In-vivo ultrasonic spectrum analysis techniques and 3-D scanning are used together with histopathology and biologic assays to characterize induced in-vivo changes in human tumor explants. Remote temperature estimations are also being investigated. Safety studies involve ultrasonic pulsed Doppler exposures of the eye, with particular attention to the potential for thermal damage in the absorptive, avascular ocular lens. Very-high-frequency ultrasound systems, which can resolve fine-scale microstructures (e.g., 30-microM dimensions), are also under study; these systems apply frequencies (e.g., 50 MHz and above) that are much higher than those previously used in biological-effects experiments. The combined use of these systems with contrast agents will also be investigated from a safety perspective. Safety will be experimentally investigated by employing these techniques in animal eyes with comprehensive follow-up examinations. A theoretical model for safety will be established. These studies are intended to identify procedures and design criteria needed to support the continued development and safe use of modern ultrasonic capabilities. This program will result in a comprehensive data base and a validated model of ultrasonic effects for extrapolating results to humans. The model will also provide fundamental information regarding non-invasive tumor therapy and diagnostic safety for a broad spectrum of medical applications.